Cannabidiol and Management of Endometriosis Pain

Sponsor

Milton S. Hershey Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04527003

Collaborator

(none)

Enrollment

Location

Arms

29.9

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators are looking to conduct a study looking at the effects of cannabidiol (CBD) in patients with endometriosis. It is believed that CBD will improve both pain and quality of life. The study will last a total of 12 weeks and involve several onsite visits in addition to daily pain assessments.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis CBD Pelvic Pain	Drug: Cannabidiol (CBD) Extract Drug: Norethindrone Acetate Other: Placebo	Phase 3

Detailed Description

The proposal is to conduct a randomized double-blind placebo-controlled pilot study to evaluate the effectiveness of cannabidiol on the management of endometriosis-related pain.

Subjects will be pre-screened from new and existing patients as well as from referral sites for the diagnosis of endometriosis. Potential subjects will be pre-screened for moderate to severe endometriosis associated pain (VAS > 3) greater than 6 months. Those meeting all inclusion and exclusion criteria that who are willing to participate will receive a detailed history and physical exam, appropriate bloodwork and undergo informed consented at the Screening Visit. Baseline survey data will be collected. During Screening, the patient's will be asked to complete their daily electronic diaries and screened for daily reporting adherence.

Randomized subjects will receive either (1) placebo (2) low dose CBD (3) high dose CBD. This study will include an 8-week intervention period during which subjects will be asked to record daily electronic VAS scores, pain medication use and a number of other parameters. Subjects will return at week 12 for a 4 week post-treatment visit, where they can also chose to enroll in an optional pharmacokinetic study. Participants will complete the Endometriosis Health Profile-30 (EHP-30), Patient Global Assessments (PGAs), the Patient Global Impression of Change (PGIC) surveys and, if partnered and sexually active, the Female Sexual Function Index at various time points. Patients will also have bloodwork done to assess for circulating markers of inflammation, circulating CBD concentration levels and liver dysfunction throughout the study duration. Subjects will be screened for side effects and asked to record pain medication use throughout the duration of the study. Study drug compliance will be assessed.

At the completion of the study, all subjects will be offered the opportunity to do pharmacokinetic testing with sublingual CBD until a maximum number of 4 patients are enrolled. The testing will include 24 hours of monitoring with sequential blood draws to determine the pharmacokinetic parameters of sublingual CBD after administration and one salivary pH. They will be discharged at 24 hours and asked to return to the clinic at 48 hours for one final lab draw.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Double-blind of study team (PI, Sub-I's and all research staff) and subjects. Randomization will be completed by Investigational Pharmacy and will keep the blind.

Primary Purpose:

Treatment

Official Title:

A Randomized Controlled Pilot Study of the Use of Cannabidiol in the Management of Endometriosis Pain

Actual Study Start Date :

Dec 4, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Group A - Placebo Norethindrone acetate (5mg daily) + Placebo	Drug: Norethindrone Acetate Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation. Other: Placebo a substance or treatment which is designed to have no therapeutic value
Active Comparator: Group B - Low Dose CBD Norethindrone acetate (5mg daily) + Low dose CBD (10mg sublingual daily)	Drug: Cannabidiol (CBD) Extract Cannabis is a well-known plant that contains more than 500 identified phytochemicals of which over 100 are cannabinoids. The most widely studied is 9-tetrahydrocannabinol (9-THC), which is the major psychoactive component of Cannabis, but Cannabidiol (CBD) has been increasingly favored for its reduced side effect profile and potential health benefits. CBD was first isolated from Cannabis in the 1940s. CBD, unlike 9-THC, does not bind to CB1 and CB2 receptors, which accounts for its lack of typical psychotropic effects, but is still appears to work via alternative mechanisms via the endocannabinoid system. Drug: Norethindrone Acetate Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.
Active Comparator: Group C - High Dose CBD Norethindrone acetate (5mg daily) + High dose CBD (20mg sublingual daily)	Drug: Cannabidiol (CBD) Extract Cannabis is a well-known plant that contains more than 500 identified phytochemicals of which over 100 are cannabinoids. The most widely studied is 9-tetrahydrocannabinol (9-THC), which is the major psychoactive component of Cannabis, but Cannabidiol (CBD) has been increasingly favored for its reduced side effect profile and potential health benefits. CBD was first isolated from Cannabis in the 1940s. CBD, unlike 9-THC, does not bind to CB1 and CB2 receptors, which accounts for its lack of typical psychotropic effects, but is still appears to work via alternative mechanisms via the endocannabinoid system. Drug: Norethindrone Acetate Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.

Arm

Intervention/Treatment

Placebo Comparator: Group A - Placebo

Norethindrone acetate (5mg daily) + Placebo

Drug: Norethindrone Acetate

Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.

Other: Placebo

a substance or treatment which is designed to have no therapeutic value

Active Comparator: Group B - Low Dose CBD

Norethindrone acetate (5mg daily) + Low dose CBD (10mg sublingual daily)

Drug: Cannabidiol (CBD) Extract

Cannabis is a well-known plant that contains more than 500 identified phytochemicals of which over 100 are cannabinoids. The most widely studied is 9-tetrahydrocannabinol (9-THC), which is the major psychoactive component of Cannabis, but Cannabidiol (CBD) has been increasingly favored for its reduced side effect profile and potential health benefits. CBD was first isolated from Cannabis in the 1940s. CBD, unlike 9-THC, does not bind to CB1 and CB2 receptors, which accounts for its lack of typical psychotropic effects, but is still appears to work via alternative mechanisms via the endocannabinoid system.

Drug: Norethindrone Acetate

Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.

Active Comparator: Group C - High Dose CBD

Norethindrone acetate (5mg daily) + High dose CBD (20mg sublingual daily)

Drug: Cannabidiol (CBD) Extract

Drug: Norethindrone Acetate

Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.

Outcome Measures

Primary Outcome Measures

Pain Score [8 weeks]
Pain will be reported daily using the Visual Analog Scale, a 100mm horizontal line on which the patient's pain intensity is represented by a point between the extremities of 0 (no pain) and 100 (worst pain). The primary study endpoint will be compared between groups using the area under the curve.

Secondary Outcome Measures

Change in Total FSFI Score [Baseline and 12 weeks]
The Female Sexual Function Index (FSFI) is a validated survey. The total FSFI score ranges from 2 (low sexual function) to 36 (high sexual function).
Change in EHP-30 Core Domain [Baseline and 12 weeks]
The Endometriosis Health Profile-30 (EHP-30) is a validated questionnaire measuring quality of life in women with endometriosis. A summary score is calculated for the core domain on a scale of 0 to 100 (0 indicates the best possible health status whereas 100 indicates the worst possible health status).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Females ages 18-45 years at the time of enrollment
A surgical diagnosis with direct visualization and/or histopathologic confirmation of endometriosis with associated moderate to severe endometriosis related pain ( > 3 on a VAS)
Is not expected to undergo gynecological surgery or other surgical procedure for treatment of endometriosis during the study period
Agrees to use approved contraception during the entire study if not surgically sterile
Patients using oral contraceptives, vaginal ring, injectable progesterone and/or GnRH agonists/antagonist for contraception and/or management of endometriosis, can be included if both they and their primary provider agree to stopping their medication and transitioning to Norethindrone acetate (NETA) as the primary treatment of endometriosis throughout the study period.
Patients using Long-acting reversible contraceptives (LARCs) for contraception and/or management of endometriosis can be included if both they and their primary provider agree to initiate Norethindrone (NETA) as the primary treatment of endometriosis throughout the study period

Exclusion Criteria:

Women that are pregnant, breastfeeding or trying to conceive
Women with chronic daily opioid use and any chronic pain or frequently reoccurring pain condition, other than endometriosis, that is treated with opioids for > 14 days per month.
Women that are currently using Cannabis based products or have used them within 30 days of enrollment
Non-English speaking or inability to read and understand English
Women with a BMI > 35 kg/m2
Women with known liver disease, such as hepatitis, or with screening LFTS (AST/ALT) > 3 times above the upper limits of normal (ULN) in the past year
Women with chronic alcohol use (defined as > 3 drinks per day, averaged over one week)
Women with chronic use of drugs (defined as > 10 days/month) that cause somnolence/sedation such as benzodiazepines or Central Nervous System (CNS) depressants that are unwilling or unable to discontinue the medications for the washout period and the duration of the study
Women who are currently taking Clobazam or Valproate and are unwilling/unable to discontinue the medication for the washout period and the duration of the study
Women with suicidal ideation or uncontrolled depression within the past year
Known history of or suspected breast cancer on screening physical exam
History of or active deep venous thrombosis or pulmonary embolism
History of or active arterial thromboembolic event (e.g. stroke, myocardial infarction)
Multiple (> 3) risk factors for arterial vascular disease (e.g. uncontrolled hypertension, diabetes mellitus, hypercholesterolemia, obesity and smoking)
Current use of a progestin-containing contraceptive implant